PI3K/AKT signaling pathway activation in a rat model of migraine.

The present study aimed to investigate phosphatidylinositol 4,5-bisphosphate 3­kinase (PI3K)/protein kinase B (AKT) signaling pathway activation in a rat model of migraine. A total of 60 male Sprague­Dawley rats were randomly divided into three groups: Blank control; suspension control; and migraine model. The model group was subcutaneously injected with a glyceryl trinitrate suspension, using an optimized Tassorelli method to establish a rat model of migraine. The activation status of the PI3K/AKT signaling pathway was assessed via measurement of the phosphorylated (p)­AKT level. The level of serum 5­hydroxytryptamine was detected using an ELISA. The mRNA and protein expression levels of PI3K and AKT, and protein levels of p­AKT were detected by reverse transcription quantitative polymerase chain reaction and western blot analysis. Expression of the PI3K gene was significantly increased (P<0.01) 6­24 h following the glyceryl trinitrate injection. There was no significant difference in the expression of AKT between any of the groups at any time. Expression of p­AKT (S473) was significantly increased in the migraine model group (P<0.01) compared with the controls groups. Immunohistochemical analysis indicated that phosphatase and tensin homolog (PTEN) continuously decreased in the migraine model group during 1­12 h, however this was only significant in the 12 h group. Levels of PTEN had increased again by 24 h. Glycogen synthase kinase (GSK)­3ß expression exhibited a similar expression pattern to PTEN. The results indicated that the PI3K/AKT signal pathway may be activated in the brain tissue of the rat migraine models. The inhibition of PTEN, which is an upstream modulator of the PI3K/AKT signaling pathway, may enhance the activation of phosphatidylinositol­3,4,5­triphosphate, thus inhibiting the expression of GSK-3ß.